This application represents the Clinical Coordinating Center of the overall proposal. Patients with acute chest pain and normal or non-diagnostic electrocardiograms (ECGs) represent a cohort whose management is notably inefficient and diagnostically challenging. Typical diagnostic testing that would allow physicians to rule out the occurrence of myocardial ischemia (e.g. nuclear imaging, echocardiography, and exercise treadmill ECG) is often not available for the initial emergency department (ED) evaluation, most of these patients are hospitalized for 24 to 36 hours to exclude the presence of acute coronary syndrome (ACS). Of the six million acute chest pain patients admitted each year in the U.S. under these conditions, <10% ultimately receive a diagnosis of ACS. Moreover, inpatient care for negative evaluations imparts an economic burden in excess of $8 billion annually. Recent advances in cardiac computed tomography (CT) technology allow for accurate detection of coronary atherosclerotic plaque and stenosis, and also allow physicians to assess global and regional LV function. Blinded observational studies demonstrate that absence of coronary atherosclerotic plaque as detected by cardiac CT is a powerful predictor of the absence of ACS (negative predictive value [NPV] of 100%). Thus, the implementation of cardiac CT in the early ED triage process may enable immediate and safe discharge of a significant fraction of acute chest pain patients without further testing. However, it is equally important to determine the effect of cardiac CT on the management of admitted patients, in particular the length of hospital stay, the number of invasive coronary angiograms, and coronary revascularizations. The growing availability of cardiac CT in EDs across the U.S. expands the opportunities for its clinical application, but also heightens the need to define its appropriate use in the evaluation of patients with acute chest pain. To address this need, we propose to perform a rigorous and adequately powered randomized diagnostic trial in 1000 subjects with low to intermediate likelihood of ACS to determine the efficiency of integrating cardiac CT, along with the information it provides on coronary artery disease (CAD) and left ventricular (LV) function, into the diagnostic workup of patients with acute chest pain. Patients will be randomized to receive the standard ED triage or the standard ED triage supplemented with a cardiac CT. Subjects will either be admitted or discharged. Admitted subjects will undergo further evaluation and testing. We will then determine whether CT increases the rate of direct ED discharges, decreases the length of hospital stay while not increasing the number of invasive coronary angiograms. To critically evaluate whether cardiac CT is also cost-effective, we will compare the 30-day costs for each strategy and subsequently perform decision and economic Markov modeling to estimate quality adjusted life expectancy and life-time medical costs of the two strategies. Overall, we hope this trial will provide a definitive answer as to whether cardiac CT can be efficiently used to discharge patients directly from the ED and clarify whether an AHA/ACC class IA recommendation is justified. Public Health Relevance: Cardiac CT technology will soon become available to most emergency departments in the United States. While some experts already promote the use of cardiac CT in patients with acute chest pain, only an adequately designed and powered multi-center randomized diagnostic trial will provide evidence whether the use of cardiac CT is justified because it is equally safe but more effective than standard care. Optimally this study will provide professional societies with adequate information to justify recommendations on the use of cardiac CT (i.e. by issuing a class IA recommendation) in the ED evaluation of patients with acute chest pain.